Making Strides Against Pancreatic Cancer

At the Podium – January 2007

By David Linehan, MD

The American Cancer Society estimates that in 2006, 33,730 Americans will be diagnosed with pancreatic cancer, and approximately 32,300 will die of the disease. That staggering mortality rate makes pancreatic cancer the fourth most common cause of cancer death in the country.

There are two main reasons for pancreatic cancer’s poor prognosis. First, it is an exceedingly difficult cancer to diagnose. By the time symptoms begin to appear – such as jaundice, pain in the abdomen or middle back, weight loss, digestive problems or a swollen gallbladder – the cancer usually is well-advanced. In fact, about 85 percent of patients have metastatic disease at the time of diagnosis.

Second, progress in treating pancreatic cancer has been exceedingly slow. In terms of research funding, pancreatic cancer has not kept pace with other cancers, such as breast and prostate cancer. Part of the reason is that unlike these cancers, there are few survivors of pancreatic cancer to champion the cause.

Fortunately, funding for research into the causes, early detection and treatment of pancreatic cancer is on the rise. Since these research endeavors are our only hope for making a difference in the lives of patients, I adhere to a basic philosophy: Every patient with pancreatic cancer should be enrolled in a clinical trial in order to study new treatments. Despite the urgent need for participants, only 10 percent to 15 percent of patients with pancreatic cancer in the United States are enrolled in these types of vital treatment studies.

At the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, we are continually investigating new combinations of therapies designed to advance care. For instance, a recently completed study using a combination of chemotherapy, radiation therapy and immunotherapy showed promise for improving survival rates in patients who had their tumors resected. Another trial is focusing on a novel agent injected into locally advanced but nonmetastatic tumors in order to improve the likelihood of a complete resection at the time of surgery. Several other trials are using new combinations of systemic chemotherapy agents in patients with stage IV disease.

The comparatively low number of patients with pancreatic cancer combined with the disease’s often deadly outcome results in another imperative: Patients with pancreatic cancer should receive treatment at centers with a high level of experience. At Siteman, our surgeons perform between 100 and 150 Whipple procedures each year, making us one of the highest volume centers for this type of surgery nationwide. The procedure, the most common operation for pancreatic cancer, involves removal of the pancreas, a portion of the stomach, the duodenum, common bile duct, gallbladder and surrounding lymph nodes. Although it is a major operation with a high risk of complications, in a study of 185 Whipples performed by Siteman surgeons, not a single death was reported.

Even when patients do well with surgery, two-thirds of them develop recurrent disease – a significant portion of them before we can start adjuvant therapy that includes chemotherapy and radiation. And of all patients with pancreatic cancer, just 15 percent of them are even candidates for surgery because most present with metastatic disease.

And therein lies the most important factor for increasing pancreatic cancer survival rates – early detection. I believe that if we can discover biomarkers for pancreatic cancer in patients’ blood, we can develop a test for early detection of the disease. Not only would cancer be discovered before it becomes incurable and metastasizes, but giving the test to patients before surgery could show metastatic disease not detectable with other diagnostic tests.

Toward that end, I am working with R. Reid Townsend, MD, PhD, director of Siteman’s Proteomics Core, on an innovative study that could help identify pancreatic cancer biomarkers in the blood. Proteomics, an emerging science that involves the study of protein structures and functions, is instrumental in discovering proteins that serve as biomarkers of disease. By drawing peripheral blood from patients with pancreatic cancer before surgery and then at three and 12 months after surgery, we hope to pinpoint proteins that are present before the tumor is removed, disappear after surgery and then reappear when the cancer returns. Although we haven’t as yet validated a biomarker for pancreatic cancer, we have a number of candidates. And that gives us hope for an eventual early detection test.

Another exciting area of research focuses on white blood cells called regulatory T cells, or T reg cells. Several years ago, we found that T reg cells are much more prevalent in patients with breast and pancreatic cancer than in healthy patients. We now have learned that pancreatic tumors hide from the body’s immune surveillance by surrounding themselves with T reg cells, making it hard for the immune system to detect them. With this knowledge, we currently are looking at ways to interfere with tumor recruitment of T reg cells. Ultimately, we would like to pair T reg depletion with an anti-cancer vaccine to evoke an immune response.

It is this type of research coupled with the willingness of patients to enroll in clinical trials of new therapies that will advance the early detection and successful treatment of pancreatic cancer.

David Linehan, MD, is associate professor of surgery, Division of General Surgery, Section of Hepatobiliary, Pancreatic and Gastrointestinal Surgery, at Washington University School of Medicine.